Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214 Journal Article
| Authors: | Mantia, C. M.; Jegede, O. A.; Plimack, E. R.; Powles, T.; Motzer, R. J.; Tannir, N. M.; Lee, C. H.; Tomita, Y.; Voss, M. H.; Choueiri, T. K.; Rini, B. I.; Hammers, H. J.; Escudier, B.; Albigès, L.; Rosenblatt, L.; Atkins, M. B.; Regan, M. M.; McDermott, D. F. |
| Article Title: | Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214 |
| Abstract: | Background Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures. Methods Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method. Results At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs. Conclusions Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN. © Author(s) (or their employer(s)) 2024. |
| Keywords: | adult; cancer survival; controlled study; protein expression; aged; middle aged; survival analysis; survival rate; overall survival; clinical trial; mortality; sunitinib; follow up; antineoplastic agent; ipilimumab; tumor volume; randomized controlled trial; antineoplastic combined chemotherapy protocols; pathology; renal cell carcinoma; kidney neoplasms; nephrectomy; survival time; liver metastasis; kidney tumor; carcinoma, renal cell; kidney cancer; drug therapy; programmed death 1 ligand 1; bootstrapping; nivolumab; humans; human; male; female; article; neutrophil lymphocyte ratio; treatment free survival |
| Journal Title: | Journal for ImmunoTherapy of Cancer |
| Volume: | 12 |
| Issue: | 7 |
| ISSN: | 2051-1426 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2024-07-01 |
| Start Page: | e009495 |
| Language: | English |
| DOI: | 10.1136/jitc-2024-009495 |
| PUBMED: | 39060019 |
| PROVIDER: | scopus |
| PMCID: | PMC11284827 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF-- Source: Scopus |
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